Oxford open neuroscience最新文献

To faithfully transmit and decode signals released from presynaptic termini, postsynaptic compartments of neuronal synapses deploy hundreds of various proteins. In addition to distinct sets of proteins, excitatory and inhibitory postsynaptic apparatuses display very different organization features and regulatory properties. Decades of extensive studies have generated a wealth of knowledge on the molecular composition, assembly architecture and activity-dependent regulatory mechanisms of excitatory postsynaptic compartments. In comparison, our understanding of the inhibitory postsynaptic apparatus trails behind. Recent studies have demonstrated that phase separation is a new paradigm underlying the formation and plasticity of both excitatory and inhibitory postsynaptic molecular assemblies. In this review, we discuss molecular composition, organizational and regulatory features of inhibitory postsynaptic densities through the lens of the phase separation concept and in comparison with the excitatory postsynaptic densities.

Synaptic plasticity in the hippocampal Cornu Ammonis (CA) subfield, CA2, is tightly regulated. However, CA2 receives projections from several extra-hippocampal modulatory nuclei that release modulators that could serve to fine-tune plasticity at CA2 synapses. Considering that there are afferent projections from the serotonergic median raphe to hippocampal CA2, we hypothesized that the neuromodulator serotonin (5-hydroxytryptamine; 5-HT) could modulate CA2 synaptic plasticity. Here, we show that bath-application of serotonin facilitates the persistence of long-term depression (LTD) at the CA3 Schaffer collateral inputs to CA2 neurons (SC-CA2) when coupled to a weak low frequency electrical stimulation, in acute rat hippocampal slices. The observed late-LTD at SC-CA2 synapses was protein synthesis- and N-methyl-D-aspartate receptor (NMDAR)-dependent. Moreover, this late-LTD at SC-CA2 synapses paves way for the associative persistence of transient forms of LTD as well as long-term potentiation to long-lasting late forms of plasticity through synaptic tagging and cross-tagging respectively, at the entorhinal cortical synapses of CA2. We further observe that the 5-HT-mediated persistence of activity-dependent LTD at SC-CA2 synapses is blocked in the presence of the brain-derived neurotrophic factor scavenger, TrkB/Fc.

The formation of a functional circuitry in the central nervous system (CNS) requires the correct number and subtypes of neural cells. In the developing brain, neural stem cells (NSCs) self-renew while giving rise to progenitors that in turn generate differentiated progeny. As such, the size and the diversity of cells that make up the functional CNS depend on the proliferative properties of NSCs. In the fruit fly Drosophila, where the process of neurogenesis has been extensively investigated, extrinsic factors such as the microenvironment of NSCs, nutrients, oxygen levels and systemic signals have been identified as regulators of NSC proliferation. Here, we review decades of work that explores how extrinsic signals non-autonomously regulate key NSC characteristics such as quiescence, proliferation and termination in the fly.

Translational neuroscience is committed to generating discoveries in the laboratory that ultimately can improve human lives. Optogenetics has received considerable attention because of its demonstrated promise in rodent brains to manipulate cells and circuits. In a recent report, Tremblay et al. [28] introduce an open resource detailing optogenetic studies of the nonhuman primate (NHP) brain and make robust claims about the translatability of the technology. We propose that their quantitative (e.g. a 91% success rate) and theoretical claims are questionable because the data were analyzed at a level relevant to the rodent but not NHP brain. Injections were clustered within a few monkeys in a few studies in a few brain regions, and their definitions of success were not clearly relevant to human neuropsychiatric disease. A reanalysis of the data with a modified definition of success that included a behavioral and biological effect revealed a 62.5% success rate that was lower when considering only strong outcomes (53.1%). This calls into question the current efficacy of optogenetic techniques in the NHP brain and suggests that we are a long way from being able to leverage them in 'the service of patients with neurological or psychiatric conditions' as the Tremblay report claims.

There has been a disproportionate increase in fluoxetine (FLX) prescription rates within the juvenile population. Thus, we evaluated how adolescent FLX exposure alters expression/phosphorylation of proteins from the extracellular signal regulated kinase (ERK)-1/2 cascade within the adult prefrontal cortex (PFC). Male Sprague-Dawley rats were exposed to FLX (20 mg/kg) for 15 consecutive days (postnatal-day [PD] 35-49). At PD70 (adulthood), we examined protein markers for ERK1/2, ribosomal S6 kinase (RSK), and mammalian target of rapamycin (mTOR). FLX-pretreatment decreased body weight, while increasing PFC phosphorylation of ERK1/2 and RSK, as well as total mTOR protein expression in adulthood. We provide first-line evidence that juvenile FLX-pretreatment induces long-term decreases in body weight-gain, along with neurobiological changes in the adult PFC - highlighting that early-life antidepressant exposure increases ERK-related signaling markers in later life.